Abstract
Epilepsy, a neurological disease characterized by recurrent seizures, is a result of increased excitatory signaling in the brain. While there are antiseizure medications available, a third of epilepsy patients experience a resistance to those treatments. Researchers have turned to investigating non-pharmacological therapies for drug-resistant epilepsy (DRE). Viral delivery of a signaling protein Semaphorin 4D (Sema4D) into the mouse hippocampus (IHC injection) has been previously shown to increase inhibitory tone and decrease seizure burden. This study investigates the efficacy of an intracerebroventricular (ICV) injection method of the Sema4D virus in reducing seizure severity in mice. ICV delivery, where the virus is stereotactically injected into the lateral ventricles, is a more traceable and translatable method for viral delivery in humans. Seizures were analyzed in adult C57BL/6 mice injected with the Sema4D viral construct or a saline-vehicle control using an electroencephalograph (EEG) and a kainic acid seizure paradigm. Mice treated with Sema4D had significantly delayed onset of status epilepticus (SE)—a seizure or a period of successive seizures that lasts longer than 5 minutes. Nevertheless, no other seizure metric was found to be significantly different between control and Sema4D-treated mice. This indicates that ICV-delivery of Sema4D, while a less invasive injection method that can prolong latency to SE, might not be the most effective in alleviating seizure severity; more research must be done to further elucidate the efficacy of the ICV-delivery of Sema4D.